Synthesis of azepine derivatives by silver-catalyzed [5+2] cycloaddition of γ-amino ketones with alkynes

Article abstract of DOI:10.1002/anie.201304902

Silver forges the ring: A new and practical silver-catalyzed [5+2] cycloaddition method has been developed for the synthesis of azepines through the formation of four new chemical bonds between a γ-amino ketone and an alkyne in one step. This method provi

Full text of DOI:10.1002/anie.201304902

Angewandte
Chemie
DOI: 10.1002/anie.201304902
Cycloaddition reactions
Synthesis of Azepine Derivatives by Silver-Catalyzed [5+2]
Cycloaddition of g-Amino Ketones with Alkynes**
Ming-Bo Zhou, Ren-Jie Song, Cheng-Yong Wang, and Jin-Heng Li*
The cycloaddition reaction is a fundamental and powerful
transformation for the construction of numerous complex
ring systems in organic synthesis.[1–5] This process is most
frequently used to prepare five- and six-membered ring
systems.[1] However, approaches using a cycloaddition strat-
egy for constructing seven-membered ring systems, particu-
larly seven-membered heterocyclic ring systems, are much
less abundant.[1–5] The difficulties of such an approach are
likely caused by a combination of entropic factors and the
presence of non-bonding interactions in the transition state.
Despite the impressive challenges in this field, the continuing
identification of bioactive natural products that contain
a seven-membered ring has led to considerable efforts to
establish valuable cycloaddition methods for their construc-
tion.[1–5] Particular focus has been put on the synthesis of
azepine derivatives,[4,5] because these are important skeletal
units that are found in numerous natural products and in
compounds with important chemical, biological, and medi-
cinal properties (Figure 1).[6]
Among the reported cycloaddition[1–5] and classical
approaches[7] toward azepine derivatives, [5+2] cycloaddition
reactions with alkynes are particularly straightforward and
highly selective; however, these transformations are quite
rare and are restricted to electron-poor alkynes.[4] In 1967,
Stogryn and Brois described a new [5+2] cycloaddition
reaction of 2,3-divinylaziridine with hexafluoro-2-butyne
to synthesize the corresponding azepine at room temperature
[Scheme 1a].[4a] Subsequently, Hassner and co-workers
Scheme 1. The [5+2] cycloaddition reaction with alkynes. Ts=Tosyl.
extended the scope of the [5+2] cycloaddition reaction to
another electron-deficient alkyne, dimethyl acetylenedicar-
boxylate, which was converted even at À208C.[4b] In 2002,
Wender and co-workers first reported an efficient transition-
metal-catalyzed hetero-[5+2] cycloaddition of cyclopropyl
imines with dimethyl acetylenedicarboxylate, leading to
dihydroazepine compounds [Scheme 1b].[4c] Thus, the devel-
opment of a general and convenient [5+2] cycloaddition using
common alkynes to azepine derivatives remains highly
desirable. Herein, we report a new silver-catalyzed tandem
[5+2] cycloaddition method using simple and readily avail-
able alkynes with g-amino ketones,[8] which results in the
corresponding azepine derivatives in moderate to good yields
[Scheme 1c].[9]
Our investigations began by choosing 4-methyl-N-(4-oxo-
2,4-diphenylbutyl)benzenesulfonamide (1a) and phenylace-
tylene (2a) as the reaction partners for the optimization of the
reaction conditions (Table 1). Initially, substrate 1a was
treated with alkyne 2a and AgSbF6 (15 mol%) in CH2Cl2 at
room temperature for 72 h, providing the desired 2,3-dihydro-
1H-azepine 3 in 54% yield (entry 1). Screening revealed that
the reaction benefits from an elevated reaction temperature:
Figure 1. Examples of important azepines.
[*] M.-B. Zhou, R.-J. Song, C.-Y. Wang, Prof. Dr. J.-H. Li
State Key Laboratory of Chemo/Biosensing and Chemometrics,
College of Chemistry and Chemical Engineering, Hunan University
Changsha 410082 (China)
E-mail: jhli@hnu.edu.cn
Prof. Dr. J.-H. Li
State Key Laboratory of Applied Organic Chemistry Lanzhou
University, Lanzhou 730000 (China)
[**] We thank the Specialized Research Fund for the Doctoral Program
of Higher Education (20120161110041), the Hunan Provincial
Natural Science Foundation of China (13JJ2018), and the Natural
Science Foundation of China (21172060) for financial support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201304902.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 1: Optimization of the reaction conditions.[a]
Entry Catalyst (mol%) Solvent
T[b] [8C] t [h] Yield[c] [%]
1
2
3
4
5
6
7
8
AgSbF6 (15)
AgSbF6 (15)
AgSbF6 (15)
AgSbF6 (15)
AgSbF6 (20)
AgSbF6 (10)
–
AgBF4 (15)
AgNO3 (15)
AgOTf (15)
Cu(OTf)2 (15)
AgSbF6 (15)
AgSbF6 (15)
AgSbF6 (15)
AgSbF6 (15)
HBF4 (15)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
RT
30
50
60
50
50
50
50
50
50
50
72
48
24
24
24
24
24
24
24
24
24
24
24
24
72
24
24
24
24
54
67
86
86
85
56
0
trace
trace
10
trace
79
13
9
83
8
9
10
11
12
13
14
15[d]
16
17
18
19[e]
CH2ClCH2Cl 50
toluene
MeCN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
50
50
50
50
50
50
50
HOTf (15)
HOAc (15)
AgSbF6 (15)
10
trace
trace
Scheme 2. Scope of alkynes 2. Reaction conditions: 1a (0.2 mmol), 2
(0.4 mmol), AgSbF6 (15 mol%), and CH2Cl2 (2 mL) at 508C under
argon atmosphere for 24 h. [a] Both [{RhCpCl2}2] (5 mol%) and
Cu(OAc)2 (50 mol%) were added at 708C.
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), and solvent
(2 mL) under argon atmosphere for 24 h. Some by-products, including
amine-decomposition products and an alkyne-hydration product (ace-
tophenone), were observed by GC-MS analysis. [b] The temperature of
the oil bath. [c] Yields of isolated products. [d] 1a (10 mmol, 3.935 g) and
2a (18 mmol). [e] One equivalent of NaOAc, Na2CO3, or Et3N was added
as a base.
With the optimized conditions in hand, we decided to
screen the scope of both g-amino ketones and alkynes for the
[5+2] cycloaddition (Schemes 2 and 3). As shown in
Scheme 2, this [5+2] cycloaddition method was found to be
applicable to a diverse range of terminal and internal alkynes
in the presence of 4-methyl-N-(4-oxo-2,4-diphenylbutyl)ben-
zenesulfonamide (1a) and AgSbF6. The results demonstrated
that several substituents, such as Me, F, Cl, Br, and acetyl, on
the aryl ring of the terminal alkyne were well-tolerated (4–
11); moreover, electron-rich arylalkynes were more reactive
than electron-deficient arylalkynes. Steric hindrance induced
by substituents on the aryl ring only slightly affected the
reaction. For example, substrates bearing a Me group at the
para- or ortho-position afforded the corresponding azepines 4
and 8 in 82% and 77% yield, respectively. However,
a substrate with a para-acetyl group led to a lower yield of
azepine 7 (47%). Notably, F, Cl, and Br substituents were
compatible with the optimized conditions, thereby facilitating
modifications at the halogenated positions (5, 6, and 9–11).
Both 1-ethynylnaphthalene and a heterocycle-containing
alkyne were viable substrates, which makes this method
more useful for the preparation of pharmaceuticals and
natural products (12 and 13). Using an internal alkyne,
however, the reaction gave a low yield (14). After a series of
experiments, we were pleased to find that satisfactory yields
could be obtained from internal alkynes in the presence of
AgSbF6, [{RhCpCl2}2], and Cu(OAc)2; however, instead of
the expected azepines, spirocycles 14 and 15 were obtained
The yield of azepine 3 was increased to 67% after 48 h when
the reaction was carried out at 308C (entry 2), and to 86%
after 24 h at either 508C or 608C (entries 3 and 4). These
results encouraged us to evaluate the amount of AgSbF6
employed (entries 4–6); we found that a AgSbF6 loading of
15 mol% gave the best result. Notably, the reaction does not
take place in the absence of a metal catalyst (entry 7).
Subsequently, a number of other catalysts, including AgBF4,
AgNO3, AgOTf, and Cu(OTf)2, were tested (entries 8–11).
However, they displayed rather poor catalytic activity in the
reaction. In contrast to these catalysts, AgSbF6 is generated
from HSbF6, a superacid; thus AgSbF6 has some special
properties: It is a stronger Lewis acid than the other Ag salts,
such as AgBF4, AgNO3, and AgOTf, and the silver ions are
À
attached to the SbF6 ion by fluoride bridges to form
a distorted octahedron, which avoids close Ag+/Ag+ con-
tacts.[10] Among the solvents examined, CH2ClCH2Cl was
found to be an excellent medium for the reaction (entry 12),
as the use of other solvents, including toluene and MeCN, led
to diminished yields (entries 13 and 14). A good yield can
achieved even when using a 10 mmol scale (1a), by prolong-
ing the reaction time (entry 15). Three Brønsted acids, HBF4,
TfOH, and HOAc, were used to replace AgSbF6: Both HBF4
and TfOH have low catalytic activity for the reaction, and
HOAc does not catalyze this transformation (entries 16–18).
The presence of a base completely suppressed the reaction
(entry 19).
through sp2 C H activation.[10] Unfortunately, aliphatic
À
alkynes are not viable for the current reaction.
2
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Scheme 4. Proposed reaction mechanism.
converted into three intermediates: 1) intermediate B,
obtained from nucleophilic addition of the amine to alkyne
2a, 2) intermediate C, obtained from electrophilic addition of
the carbonyl carbon to alkyne 2a, and 3) intermediate D. The
formation of intermediate D can be ruled out, as no reaction
was observed when g-amino ketone 1a was treated with
AgSbF6 in the absence of an alkyne. However, we cannot rule
out the electrophilic addition of the carbonyl carbon in
intermediate A to alkyne 2a.[11c] According to the results
presented, intermediate B may be easily obtained; an intra-
molecular cyclization of vinyl–Ag with the carbonyl group
results in intermediate E, which contains a hydroxyl sub-
stituent. Finally, dehydration of intermediate E affords the
desired azepine 3 with the aid of the Ag catalyst.
In summary, we have established a new and efficient
method for the synthesis of 2,3-dihydro-1H-azepines, through
the silver-catalyzed [5+2] cycloaddition of g-amino ketones
with alkynes. This intermolecular [5+2] cycloaddition reac-
tion has a broad substrate scope and allows the formation of
four new chemical bonds in one step, leading to seven-
membered ring systems through the release of H2O as the
only by-product. Most importantly, the significance of the
azepine skeleton as a structural element should render this
method attractive for both synthetic and medicinal chemistry,
thus paving the way for the synthesis of other complex
biologically active heterocyclic systems. Studies on the
mechanism and further applications of this silver-catalyzed
method in organic synthesis are currently underway in our
laboratory.
Scheme 3. Scope of g-amino ketones 1. Reaction conditions:
1 (0.2 mmol), 2 (0.4 mmol), AgSbF6 (15 mol%), and CH2Cl2 (2 mL) at
508C under argon atmosphere for 24–48 h.
We next set out to exploit the scope of g-amino ketones
(Scheme 3). First, the substitution effect at the 2 positon of
the g-amino ketones was examined. The results showed that
both functionalized aryl and alkyl groups were compatible
with the optimized conditions (16–22), and that electron-
deficient aryl groups lead to a lower reactivity than electron-
rich aryl groups. Whereas a p-MeC6H4 substituted g-amino
ketone furnished the desired azepine 16 in 77% yield, the
p-NO2C6H4-substituted substrate offered the corresponding
azepine 19 in 59% yield. A g-amino ketone bearing two
substituents, namely a Ph and a Me group, at the 2 position
was also converted into azepine 22 in good yield. Extensive
screening revealed that g-amino ketones bearing substituted
aryl groups in the 4 position were compatible with the
optimized conditions to react with different alkynes; thus
the desired azepines 23–26 were smoothly obtained in good
yields, and the structure of 25 was unambiguously confirmed
by single-crystal X-ray diffraction analysis (see the Support-
ing Information). Two simple aliphatic g-amino ketones were
found to successfully react with phenylacetylene (2a) and
AgSbF6, to construct azepines 27 and 28 in 67% and 71%
yield, respectively. However, substrates 1 with a N-PhCO or
a N-Me group instead of the N-Ts group, show no reactivity
under the optimized conditions (29 and 30).
Experimental Section
Typical experimental procedure for the AgSbF6-catalyzed [5+2]
cycloaddition of g-amino ketones with alkynes: g-amino ketone
1 (0.2 mmol), alkyne 2 (0.4 mmol), AgSbF6 (15 mol%), and CH2Cl2
(2 mL) were added to a Schlenk tube. The tube was then charged with
argon, and the reaction mixture was stirred at 508C for about 24–48 h,
until complete consumption of the starting material was observed, as
monitored by TLC and/or GC-MS analysis. After the reaction was
finished, the reaction mixture was washed with brine. The aqueous
phase was re-extracted with ethyl acetate. The combined organic
extracts were dried over Na2SO4, concentrated in vacuum, and the
The mechanisms outlined in Scheme 4 are proposed on
the basis of the results described above, and are supported by
data obtained from in situ monitoring of the reaction of 1a
1
with 2a by H NMR spectroscopy (Supporting Information,
Figure S1).[1–4,9,11] Initially, cleavage of the N H bond in
À
g-amino ketone 1a with Ag+ and complexation with alkyne
2a afford intermediate A; this hypothesis was supported by
in situ 1H NMR analysis.[9] Intermediate A may then be
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
resulting residue was purified by column chromatography on silica gel
(7:1 n-hexane/ethyl acetate) to afford the desired azepine product.
Aoki, C.-F. Chang, A. Sakurai, S. Tamura, S. Murakoshi, Agric.
Biol. Chem. 1978, 42, 457; j) M. Terada, M. Sano, A. I. Ishii, H.
Kino, S. Fukushima, T. Noro, Nippon Yakurigaku Zasshi 1982,
79, 93; k) Y. Ye, G.-W. Qin, R.-S. Xu, Phytochemistry 1994, 37,
1205; l) S. Jiwajinda, N. Hirai, K. Watanabe, V. Santisopasri, N.
Chuengsamarnyart, K. Koshimizu, H. Ohigashi, Phytochemistry
2001, 56, 693; for reviews on (À)-cobactin T, see: m) J. Hu, M. J.
Miller, Tetrahedron Lett. 1995, 36, 6379; n) E. Torres-Marquez, J.
Sinnett-Smith, S. Guha, R. Kui, R. T. Waldron, O. Rey, E.
Rozengurt, Biochem. Biophys. Res. Commun. 2010, 391, 63;
o) Y.-F. Song, Y. Qu, X.-P. Cao, W. Zhang, Mar. Biotechnol. 2011,
13, 868; for reviews on other azepines, see: p) A. B. Smith III,
Y. S. Cho, L. E. Zawacki, R. Hirschmann, G. R. Pettit, Org. Lett.
2001, 3, 4063; q) F. J. Villani, J. Med. Chem. 1967, 10, 497;
r) H. J. M. Gijsen, D. Berthelot, M. Zaja, B. Brone, I. Geuens, M.
Mercken, J. Med. Chem. 2010, 53, 7011; s) S. Tomasi, J. Renault,
B. Martin, S. Duhieu, V. Cerec, M. L. Roch, P. Uriac, J.-G.
Delcros, J. Med. Chem. 2010, 53, 7647.
Received: June 7, 2013
Revised: July 18, 2013
Published online: && &&, &&&&
Keywords: alkynes · g-amino ketones · azepines · cycloaddition ·
.
silver
[1] For selected reviews, see: a) K. P. C. Vollhardt, Angew. Chem.
1984, 96, 525; Angew. Chem. Int. Ed. Engl. 1984, 23, 539;
b) A. R. Katritzky, N. Dennis, Chem. Rev. 1989, 89, 827;
c) Advances in Cycloaddition, Vols. 1 – 6, JAI, Greenwich, CT,
1988 – 1999; d) W. Carruthers, Cycloaddition Reactions in
Organic Synthesis, Tetrahedron Organic Chemistry Series,
Pergamon, Elmsford, NY, 1990; e) M. Lautens, W. Klute, W.
Tam, Chem. Rev. 1996, 96, 49; f) C. P. Dell, Contemp. Org. Synth.
1997, 4, 87; g) L. Yet, Chem. Rev. 2000, 100, 2963; h) Cyclo-
addition Reactions in Organic Synthesis (Eds.: S. Kobayashi,
K. A. Jørgensen), Wiley-VCH, Weinheim, 2002; i) B. Heller, M.
Hapke, Chem. Soc. Rev. 2007, 36, 1085; j) F. Lꢀpez, J. L.
MascareÇas, Beilstein J. Org. Chem. 2011, 7, 1075.
[7] Representative classical methods for azepine synthesis: For
radical methods, see: a) L. Yet, Tetrahedron 1999, 55, 9349;
b) C. E. Masse, A. J. Morgan, J. S. Panek, Org. Lett. 2000, 2,
2571; for ring-expansion methods, see: c) T. J. V. Bergen, R. M.
Kellogg, J. Org. Chem. 1971, 36, 978; d) E. J. Kantorowski, M. J.
Kurth, Tetrahedron 2000, 56, 4317; for ring-closing methathesis
methods, see: e) M. E. Maier, Angew. Chem. 2000, 112, 2153;
Angew. Chem. Int. Ed. 2000, 39, 2073; f) P. Jakubec, A. Hawkins,
W. Felzmann, D. J. Dixon, J. Am. Chem. Soc. 2012, 134, 17482;
for nitrene insertion or diene-conjugated nitrile ylide cyclization
methods, see: g) Comprehensive Heterocyclic Chemistry, Vol. 9
(Ed.: A. R. Katritzky II), Pergamon, New York, 1996, p. 21;
metal-catalyzed cyclization: h) L. F. Tietze, R. Schimpf, Syn-
thesis 1993, 876; i) H. Ohno, H. Hamaguchi, M. Ohata, S.
Kosaka, T. Tanaka, J. Am. Chem. Soc. 2004, 126, 8744; j) V.
Lyaskovskyy, K. Bergander, R. Frçhlich, E.-U. Wꢂrthwein, Org.
Lett. 2007, 9, 1049; k) T. O. Vieira, H. Alper, Org. Lett. 2008, 10,
485; l) I. Nakamura, M. Okamoto, Y. Sato, M. Terada, Angew.
Chem. 2012, 124, 10974; Angew. Chem. Int. Ed. 2012, 51, 10816;
m) Z. Shi, C. Grohmann, F. Glorius, Angew. Chem. 2013, 125,
5503; Angew. Chem. Int. Ed. 2013, 52, 5393; for others, see: n) G.
Yin, Y. Zhu, P. Lu, Y. Wang, J. Org. Chem. 2011, 76, 8922.
[8] For reviews on g-amino carbonyl compounds, see: a) Chemistry
and Biochemistry of the Amino Acids (Ed.: G. C. Barrett),
Chapman and Hall, London, 1985; b) T. J. Marczynski, Brain
Res. Bull. 1998, 45, 341; c) J. S. Bryans, D. J. Wustrow, Med. Res.
Rev. 1999, 19, 149.
[9] For reviews on Ag-catalyzed reactions, see: a) M. Naodovic, H.
Yamamoto, Chem. Rev. 2008, 108, 3132; b) J.-M. Weibel, A.
Blanc, P. Pale, Chem. Rev. 2008, 108, 3149; c) M. ꢃlvarez-Corral,
M. MuÇoz-Dorado, I. Rodrꢄguez-Garcꢄa, Chem. Rev. 2008, 108,
3174; d) Silver in Organic Chemistry (Ed.: M. Harmata), Wiley,
Hoboken, 2010; for selected papers, see: e) M. Gao, C. He, H.
Chen, R. Bai, B. Cheng, A. Lei, Angew. Chem. 2013, 125, 7096;
Angew. Chem. Int. Ed. 2013, 52, 6958; f) J. Liu, Z. Fang, Q.
Zhang, Q. Liu, X. Bi, Angew. Chem. 2013, 125, 7091; Angew.
Chem. Int. Ed. 2013, 52, 6953; g) C. He, S. Guo, J. Ke, J. Hao, H.
Xu, H. Chen, A. Lei, J. Am. Chem. Soc. 2012, 134, 5766.
[2] For selected reviews on the [5+2] cycloaddition reaction, see:
a) H. Pellissier, Adv. Synth. Catal. 2011, 353, 189; b) K. E. O.
Ylijoki, J. M. Stryker, Chem. Rev. 2013, 113, 2244.
[3] For selected reviews on other cycloaddition reactions for the
synthesis of seven-membered rings, see: a) G. Dyker, Angew.
Chem. 1995, 107, 2407; Angew. Chem. Int. Ed. Engl. 1995, 34,
2223; b) M. Harmata, Acc. Chem. Res. 2001, 34, 595; c) M. A.
Battiste, P. M. Pelphrey, D. L. Wright, Chem. Eur. J. 2006, 12,
3438; d) H. Butenschçn, Angew. Chem. 2008, 120, 5367; Angew.
Chem. Int. Ed. 2008, 47, 5287; e) A. G. Lohse, R. P. Hsung,
Chem. Eur. J. 2011, 17, 3812.
[4] a) E. L. Stogryn, S. J. Brois, J. Am. Chem. Soc. 1967, 89, 605;
b) A. Hassner, R. DꢁCosta, A. T. McPhail, W. Butler, Tetrahe-
dron Lett. 1981, 22, 3691; c) P. A. Wender, T. M. Pedersen,
M. J. C. Scanio, J. Am. Chem. Soc. 2002, 124, 15154; d) M. M.
Montero-Campillo, E. M. Cabaleiro-Lago, J. Rodriguez-Otero,
J. Phys. Chem. A 2008, 112, 9068.
[5] For papers on other cycloaddition routes to azepine derivatives,
see: a) D. J. Anderson, A. Fiassner, J. Am. Chem. Soc. 1971, 93,
4339; b) N. D. Shapiro, F. D. Toste, J. Am. Chem. Soc. 2008, 130,
9244; c) H. Liu, X. Li, Z. Chen, W.-X. Hu, J. Org. Chem. 2012, 77,
5184; d) L. Wang, J. Huang, S. Peng, H. Liu, X. Jiang, J. Wang,
Angew. Chem. 2013, 125, 1812; Angew. Chem. Int. Ed. 2013, 52,
1768.
[6] For reviews, see: a) T. Kametani, K. Fukumoto, Heterocycles
1975, 3, 931; b) B. Renfroe, C. Harrington, G. R. Proctor,
Heterocyclic Compounds: Azepines, Wiley
& Interscience,
New York, 1984; c) C. R. Ganellin, D. J. Triggle, Dictionary of
Pharmacological Agents, Chapman & Hall/CRC, London, 1996;
for reviews on balanol and its analogues, see: d) P. Kulanthaivel,
Y. F. Hallock, C. Boros, S. M. Hamilton, W. P. Janzen, L. M.
Ballas, C. R. Loomis, J. B. Jiang, B. Katz, J. R. Steiner, J. Clardy,
J. Am. Chem. Soc. 1993, 115, 6452; e) S. Ohshima, M. Yanagi-
sawa, A. Katoh, T. Fujii, T. Sano, S. Matsukuma, T. Furumai, M.
Fujiu, K. Watanabe, K. Yokose, M. Arisawa, T. Okuda, J.
Antibiot. 1994, 47, 639; for reviews on the Freidinger lactams,
see: f) R. M. Freidinger, D. E. Verber, D. Schwenk Perlow, J. R.
Brooks, R. Saperstein, Science 1980, 210, 656; g) R. M. Frei-
dinger, D. Schwenk Perlow, D. F. Verber, J. Org. Chem. 1982, 47,
104; for reviews on stemonine and its analogues, see: h) M. Gçtz,
O. E. Edwards in The Alkaloids, Vol. 9 (Ed.: R. H. F. Manske),
Academic Press, New York, 1967, pp. 545 – 551; i) K. Sakata, K.
[10] H. Kunkely, A. Vogler, Inorg. Chem. Commun. 2004, 7, 400.
[11] Notably, the structure of 15 was unambiguously confirmed by
single-crystal X-ray diffraction analysis (see the Supporting
Information); a) F. W. Patureau, T. Besset, N. Kuhl, F. Glorius, J.
Am. Chem. Soc. 2011, 133, 2154; b) K. Muralirajan, K. Partha-
sarathy, C.-H. Cheng, Angew. Chem. 2011, 123, 4255; Angew.
Chem. Int. Ed. 2011, 50, 4169; a paper has proposed a vinyl
cation intermediate, by the first addition of a carbonyl carbon to
ꢀ
a C C bond: c) G. S. Viswanathan, M. Wang, C.-J. Li, Angew.
Chem. 2002, 114, 2242; Angew. Chem. Int. Ed. 2002, 41, 2138.
4
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Cycloaddition reactions
M.-B. Zhou, R.-J. Song, C.-Y. Wang,
J.-H. Li*
&&&& — &&&&
Synthesis of Azepine Derivatives by
Silver-Catalyzed [5+2] Cycloaddition of g-
Amino Ketones with Alkynes
Silver forges the ring: A new and practical
silver-catalyzed [5+2] cycloaddition
method has been developed for the syn-
thesis of azepines through the formation
of four new chemical bonds between ag-
amino ketone and an alkyne in one step.
This method provides a new hetero-[5+2]
cycloaddition strategy for the construc-
tion of seven-membered ring systems.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!